Perinatal outcomes associated with ICP in twin pregnancies were worse than singletons: an almost 5-year retrospective cohort study

Abstract

Background: Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of adverse perinatal outcomes leading to high perinatal morbidity and mortality. However, few studies have examined twin pregnancies complicated by ICP. To assess the perinatal outcomes of twin pregnancies with ICP, a retrospective cohort study was conducted.

Methods: A total of 633 twin pregnancies and 1267 singleton pregnancies with ICP were included. In addition, a correlation study was performed on the matched total bile acid (TBA) levels from maternal serum, fetal umbilical venous blood, and amniotic fluid of 33 twin pregnancies from twin groups.

Results: When compared to singletons, twin pregnancies with ICP had a higher risk of cesarean section (CS) (96.4% vs. 76.1%), preterm birth (PTB) (82.6% vs. 19.7%), fetal distress (2.0% vs. 1.3%), and neonatal intensive care unit (NICU) admission (23.6% vs. 5.1%), which was significantly related to increasing TBA levels (P < 0.05). In twin pregnancies with TBA ≥100 μmol/L, the incidences of CS, PTB, fetal distress, neonatal asphyxia, and meconium-stained amniotic fluid were 94.4, 100, 11.1, 5.6, and 36.1%, respectively. Furthermore, the maximum maternal TBA levels were positively correlated with TBA levels in the amniotic fluid (r = 0.61, P < 0.05) and umbilical cord blood (r = 0.44, P < 0.05), and a similar correlation was found for maternal TBA levels at delivery. TBA levels in umbilical cord blood and amniotic fluid also had a significant and positive correlation (r = 0.52, P < 0.05).

Conclusions: Twin pregnancies with ICP had a higher risk for adverse perinatal outcomes than singletons, which was associated with higher TBA levels. TBA can be transported through the placenta and is involved in uterus-placenta-fetal circulation.

Keywords: Intrahepatic cholestasis of pregnancy; Perinatal outcomes; Retrospective cohort study; Twin pregnancies.

Fig. 1

Dynamic TBA variation in twin pregnancies with ICP at various TBA levels. A Twin pregnancies with 10 ≤ TBA < 40 μmol/L. B Twin pregnancies with 40 ≤ TBA < 100 μmol/L. C Twin pregnancies with TBA ≥100 μmol/L. D All included twin pregnancies. Three different colored lines are used to depict the dynamic fluctuation of TBA in twin pregnancies with ICP during pregnancy and 5 weeks after delivery. The red line represents the maximum levels of TBA of included patients, the blue line represents the mean levels of TBA of included patients, and the yellow line represents the minimum levels of TBA of included patients

Fig. 2

TBA levels in maternal serum, umbilical venous blood, and amniotic fluid with Pearson correlation scatterplots. A The ordinate of Fig. 2-A represents TBA levels in the amniotic fluid, Fig. 2-A1 the maximum serum TBA levels (r = 0.61, P < 0.05), and Fig. 2-A2 the TBA levels upon delivery (r = 0.76, P < 0.05). B The ordinate of Fig. 2-B shows TBA levels in the umbilical venous blood, Fig. 2-B1 shows the highest serum TBA levels (r = 0.44, P < 0.05), and Fig. 2-B2 shows TBA levels at delivery (r = 0.47, P < 0.05). C The correlation of TBA levels in umbilical venous blood and amniotic fluid (r = 0.52, P < 0.05) is shown in Fig. 2-C. Significant correlations have a P value of less than 0.05

Fig. 3

Pearson correlation matrix of maternal serum TBA levels and biochemical markers in umbilical venous blood. The R package “corrgram” was used to create the Pearson correlation matrix: Create a Correlogram (Version 1.13). Using the color map, the Pearson correlation value is color-coded. Positive correlations appear in blue, while negative correlations appear in red. The circle size and color intensity are proportionate to the correlation coefficients. On the right side of the correlogram, the legend color shows the correlation coefficients and the corresponding colors. Correlations with a P value of < 0.05 are considered significant in the above graph. Figure 3‘s ordinate depicts biochemical indications of umbilical venous blood, whereas the abscissa represents the highest TBA levels and TBA levels upon delivery